Kevin L. Greason, MD, disucsses the advances in endovascular repair of thoracic aortic aneurysm.

Aneurysms affect an estimated 6 patients per 100,000 persons per year, an estimated 21,000 patients yearly in the United States. Unfortunately, these patients frequently have comorbid conditions such as chronic obstructive pulmonary disease, coronary artery disease, or renal insufficiency that can complicate standard open operative repair.

A new technology has emerged in the management of thoracic aortic aneurysm previously treated only with open surgery—the endovascular stent graft. Successful stent graft treatment of a descending thoracic aortic aneurysm has the potential to avoid the deleterious effects of a thoracotomy, aortic cross-clamp placement, and major blood loss.

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Mayo Clinic mammography screening recommendations remain the same, despite revised recommendations by the U.S. Preventive Services Task Force.

Sandhya Pruthi, M.D., director of the Breast Clinic at Mayo Clinic in Rochester, and leader of the task force explains Mayo’s recommendations.

Mayo Clinic physicians and researchers state that the modeling data used in the analysis, along with input from recent clinical trials conducted outside of the United States, do not constitute strong enough data to change Mayo’s practice.

Rodney Breau, M.D., a Mayo Clinic urologic oncology fellow discusses new Mayo Clinic research that studied the association between prostate-specific antigen levels and prostate size and found that routine annual evaluation of prostate growth is not necessarily a predictor for the development of prostate cancer. These findings were presented at the North Central Section of the American Urological Association in Scottsdale, Ariz.

ABSTRACT
Introduction: We evaluated the rate of prostate growth and the rate of change in PSA for men in a large population-based cohort.

Methods: In 1990, 616 men between 40 and 79 years of age without prostate disease were randomly selected from Olmsted County, Minnesota. Patients participated in biennial examinations for 14 years which included PSA and transrectal ultrasonographic prostate volume measurements. The ratios of longitudinal change in PSA and prostate volume were compared between groups.

Results: Of 616 men, 58 (9.4%) were diagnosed with prostate cancer. The median PSA velocity in patients with and without a prostate cancer diagnosis was 6.0%/year and 3.3%/year, respectively. In both groups of patients, median prostate volume increase was 2.2% per year. For patients who developed prostate cancer, the rate of PSA increase was 2.5 (IQR:2.0-3.3) times the rate of prostate volume increase, compared to a rate of 1.5 (IQR:0.8-2.2) for those who did not develop prostate cancer (p<0.001).

Conclusions: In a large population based cohort, men who developed prostate cancer had a similar rate of prostate growth but a disproportionate rise in PSA compared to men who did not develop prostate cancer. These results suggest that the disproportionate rise in PSA in men who develop prostate cancer is not due solely to concomitant prostatic enlargement.

Dr. Daniel Elliot discusses Robot-Assisted Laparoscopic Sacrocolpopexy. This information was recently presented at the North Central Section of the American Urological Association in Scottsdale, Ariz.

ABSTRACT
INTRODUCTION: With the advent of robotic-assisted laparoscopic surgery, application of open surgical principles is increasingly translated to the minimally invasive laparoscopic approach.

OBJECTIVES: We examined the learning curve for the robot-assisted sacrocolpopexy (RALS) as defined by operative times, mesh erosion and prolapse recurrence.

METHODS: From 2002 to 2008, 53 consecutive females with symptomatic high-grade post-hysterectomy vaginal vault prolapse underwent RALS in the Department of Urology by one surgical team. OR times and post-operative complications were collected prospectively along with patient demographics. A linear regression model was used to predict a learning curve in sequential cases.

RESULTS: With an average follow-up of 35.8 months (range 1.4 to 67), 48 females, with an average age of 66 years underwent RALS (5 conversions to open).

CONCLUSIONS: A decrease in OR time and post-operative complications is evident with more cases of RALS, regardless of patient age, when performed by one surgical team.

AUTHORS: M. A. Childs, Mayo Clinic, Rochester, MN; S. McGee, J. Routh, G. Chow, D. Elliot of Mayo Clinic

Dr. Krowka discusses a recent presentation on Portopulmonary hypertension.

ABSTRACT
Background: Ambrisentan is a newer endothelin receptor antagonist (ERA) with potential advantages over Bosentan for the therapy of POPH: selective ERA antagonism, once-daily dosing and minimizes elevation in liver enzymes. We describe hemodynamic responses and clinical outcomes of patients with POPH treated with Ambrisentan at Mayo Clinic, Rochester, MN.

Methods: We prospectively identified consecutive adult POPH patients evaluated at Mayo Clinic from January 2007 until May 2009 deemed candidates for oral pulmonary hypertension therapy. In this open label study, patients received 5 mg of Ambrisentan daily for 4 weeks with dose increase to 10 mg daily thereafter. Liver enzymes were assessed monthly. Baseline and follow-up echocardiograms and right heart catheterizations were accomplished.

Results: We identified 12 patients with POPH started on single therapy with Ambrisentan. The median age (IQR, interquartile range) was 55(52-60). Seven patients were male and 11 were Caucasian. Patients were followed for a median of 613 days (334-1011). The main etiology of portal hypertension was cirrhosis (10 cases).The most common etiology of cirrhosis was alcohol (5 cases), followed by hepatitis C (3 cases). Cirrhotic patients had a median MELD score of 10(7-12), and the majority of patients were in Child’s A classification (8 cases). Median time on Ambrisentan therapy was 390 days (206-611). Two patients died, one of advanced hepatocellular carcinoma, and one of septic shock following pneumonia. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased after therapy with Ambrisentan, with associated improvement in functional class. Transaminases and total bilirubin levels remained stable after initiation of Ambrisentan.

Conclusion: In this prospective cohort of patients with POPH, Ambrisentan proved to be efficacious with significant improvement in hemodynamics and functional class. In addition, Ambrisentan was safe with no significant elevation in transaminases or total bilirubin.

AUTHORS
Rodrigo Cartin-Ceba, Karen Swanson, Michael J. Krowka from Mayo Clinic.

Dr. Leslie Cooper Jr., discussed several new diagnostic methods, such as cardiac magnetic resonance imaging (MRI), that are useful for diagnosing myocarditis. These findings were published in the November 2009 issue of Mayo Clinic Proceedings.

Abstract
Myocarditis, an inflammatory disease of heart muscle, is an important cause of dilated cardiomyopathy worldwide. Viral infection is also an important cause of myocarditis, and the spectrum of viruses known to cause myocarditis has changed in the past 2 decades. Several new diagnostic methods, such as cardiac magnetic resonance imaging, are useful for diagnosing myocarditis. Endomyocardial biopsy may be used for patients with acute dilated cardiomyopathy associated with hemodynamic compromise, those with life-threatening arrhythmia, and those whose condition does not respond to conventional supportive therapy. Important prognostic variables include the degree of left and right ventricular dysfunction, heart block, and specific histopathological forms of myocarditis. We review diagnostic and therapeutic strategies for the treatment of viral myocarditis. English-language publications in PubMed and references from relevant articles published between January 1, 1985, and August 5, 2008, were analyzed. Main keywords searched were myocarditis, dilated cardiomyopathy, endomyocardial biopsy, cardiac magnetic resonance imaging, and immunotherapy.

Authors
Jason C. Schultz, MD, Anthony A. Hilliard, MD, Leslie T. Cooper, Jr, MD and Charanjit S. Rihal, MD from Mayo Clinic

Dr. John M. Pach, M.D., of the Department of Ophthalmology and Dr. Steven A. Smith, of the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at Mayo Clinic discuss the discuss major risk factors for diabetic retinopathy including diabetes mellitus.

Dr. Pach

Dr. Smith

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Dr. William Sandborn discusses a new study led by Mayo Clinic that found ulcerative colitis patients had a 41 percent reduction in colectomy after a year when treated with infliximab. This study is published in the October 2009 issue of Gastroenterology.

ABSTRACT
Background & Aims
The efficacy of infliximab for treating patients with ulcerative colitis has been established.

Methods
The Active Ulcerative Colitis Trial (ACT)-1 and ACT-2 randomized, double-blind, placebo-controlled studies evaluated infliximab induction and maintenance therapy in moderately to severely active ulcerative colitis. Overall, 728 patients received placebo or infliximab (5 or 10 mg/kg) intravenously at weeks 0, 2, and 6, then every 8 weeks through week 46 (ACT-1) or 22 (ACT-2). Colectomy, hospitalization, and surgery/procedure data through 54 weeks after the first infusion were obtained from ACT-1, ACT-2, and associated data sources. In the prespecified analysis, all data were combined to ascertain time to colectomy. Kaplan–Meier product-limit method was used to estimate the cumulative incidence of colectomy, and log-rank test was used to compare the combined infliximab group and placebo.

Results
Eighty-seven percent (630 of 728) of patients had complete colectomy follow-up; 13% (98 of 728) of patients had a median follow-up of 6.2 months. The cumulative incidence of colectomy through 54 weeks was 10% for infliximab and 17% for placebo (P = .02), yielding an absolute risk reduction of 7%. Compared with placebo, fewer ulcerative colitis-related hospitalizations and surgeries/procedures per 100 patient-years of treatment occurred with infliximab therapy: 40 vs 20 (P = .003) and 34 vs 21 (P = .03), respectively. Serious adverse events occurring in infliximab-treated patients included serious infections, tuberculosis, histoplasmosis, listeriosis, and malignancy.

Conclusions
Patients with moderately to severely active ulcerative colitis treated with infliximab were less likely to undergo colectomy through 54 weeks than those receiving placebo.

Conflicts of Interest The authors disclose the following: William J. Sandborn, Paul Rutgeerts, Brian G. Feagan, Walter Reinisch, Stephen B. Hanauer, Gary R. Lichtenstein, Willem J. S. de Villiers, Bruce E. Sands, and Jean Frédéric Colombel have served as consultants for and received honoraria and research grants from Centocor Ortho Biotech, Inc. Daniel Present has served as a consultant for and received a research grant from Centocor Research and Development, Inc. Jewel Johanns and Jiandong Lu are employees of Centocor Clinical Research and Development, Inc., a subsidiary of Johnson & Johnson, and own stock in Johnson & Johnson. Allan Olson is a former employee of Centocor Clinical Research and Development, Inc., is currently employed at R. W. Johnson Pharmaceutical Research and Development, and owns stock in Johnson & Johnson. Kevin Horgan is a former employee of Centocor Clinical Research and Development, Inc.

Funding Support Supported by a research grant from Centocor Research and Development, Inc, Malvern, Pennsylvania, and Schering Plough, Kenilworth, New Jersey. Supported by a grant (1-UL1-RR024150-01) from the National Center for Research Resources, a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research.

Some of the results presented in this article were published as an abstract and presented at The American College of Gastroenterology 2007 annual meeting in Philadelphia, Pennsylvania (Am J Gastroenterol 2007;102[Suppl 2]:Abs984); United European Gastroenterology Week 2007 annual meeting in Paris, France (Gut 2007;39:A26); and 2007 CCFA National Research and Clinical Conference, 6th Annual Advances in the Inflammatory Bowel Diseases in Aventura, Florida (Inflamm Bowel Dis 2007;14[Suppl 1]:AbsO-006).

Dr. Tait Shanafelt discusses a report that distress and fatigue among medical residents are independent contributors to self-perceived medical errors. The findings appear in the Journal of the American Medical Association.

ABSTRACT
JAMA. 2009;302(12):1294-1300.

Context Fatigue and distress have been separately shown to be associated with medical errors. The contribution of each factor when assessed simultaneously is unknown.

Objective To determine the association of fatigue and distress with self-perceived major medical errors among resident physicians using validated metrics.

Design, Setting, and Participants Prospective longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic, Rochester, Minnesota. Data were provided by 380 of 430 eligible residents (88.3%). Participants began training from 2003 to 2008 and completed surveys quarterly through February 2009. Surveys included self-assessment of medical errors, linear analog self-assessment of overall quality of life (QOL) and fatigue, the Maslach Burnout Inventory, the PRIME-MD depression screening instrument, and the Epworth Sleepiness Scale.

Main Outcome Measures Frequency of self-perceived, self-defined major medical errors was recorded. Associations of fatigue, QOL, burnout, and symptoms of depression with a subsequently reported major medical error were determined using generalized estimating equations for repeated measures.

Results The mean response rate to individual surveys was 67.5%. Of the 356 participants providing error data (93.7%), 139 (39%) reported making at least 1 major medical error during the study period. In univariate analyses, there was an association of subsequent self-reported error with the Epworth Sleepiness Scale score (odds ratio [OR], 1.10 per unit increase; 95% confidence interval [CI], 1.03-1.16; P = .002) and fatigue score (OR, 1.14 per unit increase; 95% CI, 1.08-1.21; P < .001). Subsequent error was also associated with burnout (ORs per 1-unit change: depersonalization OR, 1.09; 95% CI, 1.05-1.12; P < .001; emotional exhaustion OR, 1.06; 95% CI, 1.04-1.08; P < .001; lower personal accomplishment OR, 0.94; 95% CI, 0.92-0.97; P < .001), a positive depression screen (OR, 2.56; 95% CI, 1.76-3.72; P < .001), and overall QOL (OR, 0.84 per unit increase; 95% CI, 0.79-0.91; P < .001). Fatigue and distress variables remained statistically significant when modeled together with little change in the point estimates of effect. Sleepiness and distress, when modeled together, showed little change in point estimates of effect, but sleepiness no longer had a statistically significant association with errors when adjusted for burnout or depression.

Conclusion Among internal medicine residents, higher levels of fatigue and distress are independently associated with self-perceived medical errors.

Authors Colin P. West, MD, PhD; Angelina D. Tan, BS, BA; Thomas M. Habermann, MD; Jeff A. Sloan, PhD; Tait D. Shanafelt, MD from Mayo Clinic, Rochester, Minnesota.

This study was presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Dusseldorf, Germany, on Sept. 11, 2009, and found that two genes in mice were associated with good central nervous system repair in multiple sclerosis (MS). This early research holds promise for new therapies and better prediction of patient outcomes.

Allan Bieber, Ph.D., a Mayo Clinic neuroscientist and author of the study explains: “Most MS genetic studies have looked at disease susceptibility — or why some people get MS and others do not. This study asked, among those who have MS, why do some do well with the disease while others do poorly, and what might be the genetic determinants of this difference in outcome.”

According to Dr. Bieber, the research suggests that there may be a small number of strong genetic determinants for central nervous system repair following demyelinating disease, rather than a larger number of weak determinants.

Abstract
Clinical experience with humans who have multiple sclerosis and work with animal models of demyelinating disease, has demonstrated that significant CNS repair can occur after demyelination even without therapeutic intervention. However, for reasons that are poorly understood, repair often fails or is incomplete. Recently we have investigated the genetic regulation of CNS repair and remyelination in the Theiler’s murine encephalomyelitis virus (TMEV) model of demyelinating disease. We have found marked differences in spontaneous repair in different strains of mice ranging from minimal repair and the progressive accumulation of neurologic deficits in B10.Q mice, to extensive spontaneous myelin repair with axonal and functional preservation in FVB mice. The “reparative phenotype” of the FVB strain is inherited as a dominant trait in outcrosses with the non-repairing B10.Q strain. To better understand the molecular mechanisms of endogenous CNS repair, we have mapped genetic loci that are responsible for the reparative phenotype. Using single nucleotide polymorphisms (SNPs) as genetic markers, we have detected two very strong quantitative trait loci (QTLs) for CNS repair, one on chromosomes 3 (LOD~15) and one on chromosome 9 (LOD~21). The mouse genes for epidermal growth factor (EGF), a key regulator of cell growth and development, and Tyk 2, a janus kinase that plays a central role in controlling the TH1 immune response, present themselves as potential candidate genes for the QTLs on chromosomes 3 and 9 respectively. We have identified polymorphisms between the FVB and B10.Q strains in the protein coding sequences of both EGF and Tyk2 which support their roles as candidate genes. Relatively little is known about the genetics of CNS repair and these studies begin to identify the molecular pathways that are central to this poorly understood process.

Authors
Kanitta Suwansrinon, MD; Allan J. Bieber, PhD; Moses Rodriguez, MD all from Mayo Clinic

Multiple Sclerosis Treatment at Mayo Clinic
Multiple Sclerosis Research at Mayo Clinic